tbuckley/cabot-search huggingface dataset:
How to use quality indicators for antimicrobial stewardship in your hospital: a practical example on outpatient parenteral antimicrobial therapy
Authors: Ralf Stemkens, Jeroen A. Schouten, Sophie A.M. van Kessel, Reinier P. Akkermans, Denise S.C. Telgt, Hanneke W.H.A. Fleuren, Mark A.A. Claassen, Marlies E.J. L. Hulscher, Jaap ten Oever
Journal: Clinical Microbiology and Infection (2022)

Antimicrobial stewardship (AMS) teams are responsible for performing an AMS programme in their hospitals that aims to improve the quality of antibiotic use. Measuring the quality of antimicrobial use is a core task of a stewardship team. Measurement provides insight into the current quality of antibiotic use and allows for the establishment of goals for improvement. Yet, a practical description of how such a quality measurement using quality indicators (QIs) should be performed is lacking.To provide practical guidance on how a stewardship team can use QIs to measure the quality of antibiotic use in their hospital and identify targets for improvement.General principles from implementation science, peer-reviewed publications, and experience from clinicians and researchers with AMS experience.We provide step-by-step guidance on how AMS teams can use QIs to measure the quality of antibiotic use. The principles behind each step are explained and illustrated with the description and results of an audit of patients receiving outpatient parenteral antimicrobial therapy in four Dutch hospitals.Improving the quality of antibiotic use is impossible without first gaining insight into that quality by performing a measurement with validated QIs. This step-by-step practice example of how to use quality indicators in a hospital will help AMS teams to identify targets for improvement. This enables them to perform their AMS programme more effectively and efficiently.
Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients
Authors: Aenne Harberts, Golda M. Schaub, Darius F. Ruether, Paul M. Duengelhoef, Thomas T. Brehm, Hendrik Karsten, Anahita Fathi, Jacqueline Jahnke-Triankowski, Lutz Fischer, Marylyn M. Addo, Friedrich Haag, Marc Luetgehetmann, Ansgar W. Lohse, Julian Schulze zur Wiesch, Martina Sterneck
Journal: Clinical Gastroenterology and Hepatology (2022)
Hepatitis B RNA and Core-Related Antigen Provide Value Beyond DNA in Evaluating e But Not Surface Antigen Clearance
Authors: Wendy C. King, Richard K. Sterling, Amanda S. Hinerman, Anna S.F. Lok, Gavin A. Cloherty, Marc G. Ghany, Abdus S. Wahed, Raymond T. Chung, Harry L.A. Janssen, Mandana Khalili, Daryl T.Y. Lau, William M. Lee, Mauricio Lisker-Melman, Norah Terrault
Journal: Clinical Gastroenterology and Hepatology (2022)
Targeting inflammatory monocytes by immune-modifying nanoparticles prevents acute kidney allograft rejection
Authors: Christina Lai, Steven J. Chadban, Yik Wen Loh, Tony King-Tak Kwan, Chuanmin Wang, Julian Singer, Paula Niewold, Zheng Ling, Alanna Spiteri, Daniel Getts, Nicholas Jonathan Cole King, Huiling Wu
Journal: Kidney International (2022)
Evaluation of maximal exercise capacity through the incremental shuttle walking test in lymphangioleiomyomatosis
Authors: D. Silva Queiroz, C.C.B. Marques da Silva, A. Franco Amaral, M. Rodrigues Oliveira, J.M. Salge, C.R. Ribeiro Carvalho, B. Guedes Baldi, C.R.F. Carvalho
Journal: Pulmonology (2022)

The cardiopulmonary exercise test (CPET) is the gold standard for assessing aerobic fitness; however, it is expensive, not widely available, and requires specialized equipment and staff. The incremental shuttle walking test (ISWT) is an exercise field test used to evaluate exercise capacity and may be an alternative to CPET in patients with lymphangioleiomyomatosis (LAM). To investigate whether the ISWT can be used to assess maximal aerobic capacity in patients with LAM. Forty-five women were evaluated on two days, and they randomly performed the CPET and ISWT. The maximum oxygen uptake (peak VO2) was evaluated using gas analyzers in both tests. The carbon dioxide production (VCO2), respiratory exchange ratio (RER), and heart rate (HR) were compared during peak exercise. Pearson's correlation and Bland-Altman assessed the association and agreement, respectively. The intraclass correlation coefficient (ICC) was used to assess the reliability of the data. All patients (46.1 ± 10.2 years) presented similar peak VO2, RER, and peak HR during the CPET and ISWT (15.6 ± 4.6 vs. 15.7 ± 4.4 ml·kg−1·min−1; 1.15±0.09 vs. 1.17±0.12; and 142.2 ± 18.6 vs. 141.5 ± 22.2 bpm, respectively; p>0.05). A good linear correlation (r = 0.79; p<0.001) and ICC (0.86; 95%CI 0.74−0.93) were observed between the peak VO2 in both tests. Predictive peak VO2 equations based on the ISWT performance are also presented. Our results suggest that the ISWT can be used to assess maximal exercise performance in patients with LAM, and it is a valuable option to be used as an alternative to the CPET and predict maximal exercise capacity.
A micelle-based stage-by-stage impelled system for efficient doxorubicin delivery
Authors: Sunfan Li, Fangzhou Li, Dong Wan, Zuqin Chen, Jie Pan, Xing-Jie Liang
Journal: Bioactive Materials (2022)

Chemotherapy remains the mainstay of cancer treatment, benefiting millions of patients each year, but the side effects of chemotherapy drugs severely limit their clinical use. Doxorubicin (DOX) can cause various side effects such as heart damage and treatment-related tumors. The effective use of active and passive targeting will improve the clinical application of DOX. Here, TPGS3350 and bioactive peptides were utilized to construct a micelle-based stage-by-stage impelled efficient system (missiles) for DOX delivery (DOX missiles). By taking advantage of the EPR effect, DOX missiles are efficiently enriched at the tumor site. After being cleaved by matrix metalloproteinase2 (MMP2), the peptide (VRGD) targets tumor cells to facilitate uptake of the missiles by the tumor cells via receptor-mediated endocytosis. The intracellular activated caspase-3-catalyzed explosion of DOX missiles further enables efficient tumor killing. This study provides an efficient approach for DOX delivery and toxicity reduction.
Discordance Between Coronary Artery Calcium Area and Density Predicts Long-Term Atherosclerotic Cardiovascular Disease Risk
Authors: Alexander C. Razavi, Marly van Assen, Carlo N. De Cecco, Zeina A. Dardari, Daniel S. Berman, Matthew J. Budoff, Michael D. Miedema, Khurram Nasir, Alan Rozanski, John A. Rumberger, Leslee J. Shaw, Laurence S. Sperling, Seamus P. Whelton, Martin Bødtker Mortensen, Michael J. Blaha, Omar Dzaye
Journal: JACC. Cardiovascular imaging (2022)
Cytomegalovirus infection in transplant recipients: newly approved additions to our armamentarium
Authors: Fareed Khawaja, Amy Spallone, Camille N. Kotton, Roy F. Chemaly
Journal: Clinical Microbiology and Infection (2022)

BackgroundThe burden that cytomegalovirus (CMV) portends for haematopoietic and solid-organ transplant recipients cannot be understated. Valganciclovir and ganciclovir have successfully been used for prevention and treatment of CMV infections, although with serious side effects such as leucopenia and some development of resistance. Until recently, available therapies for ganciclovir-resistant CMV have significant toxicities. Although advances have been made in the field, the unmet medical needs for effective and well-tolerated therapies are significant.ObjectivesThis review aims to summarise the current and emerging CMV antiviral drugs and discusses future perspectives in the field.Sources: We searched for relevant articles with pertinent keywords: "Cytomegalovirus OR CMV", "Transplant" and "Antiviral". Articles published after 2019 were given preference. Articles were reviewed by the authors for relevance and impact to the subject of interest.ContentWe outline in this review current advances in prophylaxis of CMV infection with letermovir, breakthrough CMV infections while on or after prophylaxis, the development of resistant and refractory CMV infections, and the newly approved anti-CMV agent, maribavir, in haematopoietic and solid-organ transplant recipients.ImplicationsPrevention of CMV infections after transplant has improved greatly over the past few years. Despite major advancements, breakthrough CMV infections and development of refractory and resistant CMV infections remain major complications post transplantation. We highlight emerging therapeutics that tolerably and effectively prevent and treat CMV infections, especially refractory and resistant cases.
Hepatitis B virus reactivation associated with new classes of immunosuppressants and immunomodulators: A systematic review, meta-analysis, and expert opinion
Authors: George V. Papatheodoridis, Vasileios Lekakis, Thodoris Voulgaris, Pietro Lampertico, Thomas Berg, Henry L.Y. Chan, Jia-Horng Kao, Norah Terrault, Anna S. Lok, K. Rajender Reddy
Journal: Journal of Hepatology (2022)
Circulating L-arginine predicts the survival of cancer patients treated with immune checkpoint inhibitors
Authors: F. Peyraud, J.-P. Guégan, D. Bodet, I. Nafia, L. Fontan, C. Auzanneau, S. Cousin, G. Roubaud, M. Cabart, F. Chomy, F. Le Loarer, N. Chaput, F.-X. Danlos, D. Planchard, C. Even, M. Khettab, L. Tselikas, B. Besse, F. Barlesi, J.-C. Soria, A. Marabelle, A. Bessede, A. Italiano
Journal: Annals of Oncology (2022)
Investigating drug resistance of Mycobacterium leprae in the Comoros: an observational deep-sequencing study
Authors: Sofie Marijke Braet, Agathe Jouet, Alexandra Aubry, Magalie Van Dyck-Lippens, Esteban Lenoir, Younoussa Assoumani, Abdallah Baco, Aboubacar Mzembaba, Emmanuelle Cambau, Sidra Ezidio Gonçalves Vasconcellos, Leen Rigouts, Philip Noel Suffys, Epco Hasker, Philip Supply, Bouke Catherine de Jong
Journal: The Lancet Microbe (2022)
Association between IgG antibody levels and adverse events after first and second Bnt162b2 mRNA vaccine doses
Authors: Eyal Braun, Netanel A. Horowitz, Ronit Leiba, Avi Weissman, Michal Mekel, Yael Shachor-Meyouhas, Khetam Hussein, Michael Halberthal, Zaher S. Azzam, Gidon Berger
Journal: Clinical Microbiology and Infection (2022)
Health-related Quality of Life Analysis from KEYNOTE-426: Pembrolizumab plus Axitinib Versus Sunitinib for Advanced Renal Cell Carcinoma
Authors: Jens Bedke, Brian I. Rini, Elizabeth R. Plimack, Viktor Stus, Rustem Gafanov, Tom Waddell, Dimitry Nosov, Frederic Pouliot, Denis Soulières, Bohuslav Melichar, Ihor Vynnychenko, Sergio J. Azevedo, Delphine Borchiellini, Raymond S. McDermott, Satoshi Tamada, Allison Martin Nguyen, Shuyan Wan, Rodolfo F. Perini, L. Rhoda Molife, Michael B. Atkins, Thomas Powles
Journal: European Urology (2022)
Ivermectin and albendazole coadministration: opportunities for strongyloidiasis control
Authors: Javier Gandasegui, Chukwuemeka Onwuchekwa, Alejandro J Krolewiecki, Stephen R Doyle, Rachel L Pullan, Wendemagegn Enbiale, Stella Kepha, Hollie Ann Hatherell, Lisette van Lieshout, María Cambra-Pellejà, Valdemiro Escola, José Muñoz
Journal: The Lancet Infectious Diseases (2022)
The impact of aerobic and resistance training intensity on markers of neuroplasticity in health and disease
Authors: Tibor Hortobágyi, Tomas Vetrovsky, Guilherme Moraes Balbim, Nárlon Cássio Boa Sorte Silva, Andrea Manca, Franca Deriu, Mia Kolmos, Christina Kruuse, Teresa Liu-Ambrose, Zsolt Radák, Márk Váczi, Hanna Johansson, Paulo Cezar Rocha dos Santos, Erika Franzén, Urs Granacher
Journal: Ageing Research Reviews (2022)

To determine the effects of low- vs. high-intensity aerobic and resistance training on motor and cognitive function, brain activation, brain structure, and neurochemical markers of neuroplasticity and the association thereof in healthy young and older adults and in patients with multiple sclerosis, Parkinson's disease, and stroke.Systematic review and robust variance estimation meta-analysis with meta-regression.Systematic search of MEDLINE, Web of Science, and CINAHL databases.Fifty studies with 60 intervention arms and 2283 in-analyses participants were included. Due to the low number of studies, the three patient groups were combined and analyzed as a single group. Overall, low- (g=0.19, p = 0.024) and high-intensity exercise (g=0.40, p = 0.001) improved neuroplasticity. Exercise intensity scaled with neuroplasticity only in healthy young adults but not in healthy older adults or patient groups. Exercise-induced improvements in neuroplasticity were associated with changes in motor but not cognitive outcomes.Exercise intensity is an important variable to dose and individualize the exercise stimulus for healthy young individuals but not necessarily for healthy older adults and neurological patients. This conclusion warrants caution because studies are needed that directly compare the effects of low- vs. high-intensity exercise on neuroplasticity to determine if such changes are mechanistically and incrementally linked to improved cognition and motor function.
Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study
Authors: Martina E McMenamin, Joshua Nealon, Yun Lin, Jessica Y Wong, Justin K Cheung, Eric H Y Lau, Peng Wu, Gabriel M Leung, Benjamin J Cowling
Journal: The Lancet Infectious Diseases (2022)
Serum HBcrAg and Hepatocellular Carcinoma in a Taiwanese Population Seronegative for HBsAg and Anti-HCV
Authors: Yi-Chung Hsieh, Mei-Hung Pan, Wen-Juei Jeng, Hui-Han Hu, Jessica Liu, Masashi Mizokami, Chien-Jen Chen, Hwai-I Yang
Journal: Clinical Gastroenterology and Hepatology (2022)

Hepatitis B core-related antigen (HBcrAg) is a surrogate seromarker of intrahepatic hepatitis B virus covalently closed circular DNA quantity and activity and a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B patients. We assess association between HBcrAg and HCC in individuals seronegative for hepatitis B surface antigen and anti-hepatitis C virus (NBNC) in Taiwan.A total of 129 newly developed HCC cases and 520 frequency-matched non-HCC controls were drawn from the REVEAL-NBNC cohort. Serum HBcrAg and other risk factors measured at recruitment were compared between cases and controls. Regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).The proportion of baseline HBcrAg positivity (≥1000 U/mL) was significantly higher in HCC cases than in controls (12.4% vs 1.4%, P < .001). In multivariate analysis, HBcrAg positivity was associated with significantly higher risk of HCC (adjusted OR [95% CI]: 9.3 [3.3-26.4]; P < .001]. The HCC population attributable to HBcrAg positivity was 11.1% (95% CI: 9.7%-12.5%).Seropositivity of HBcrAg might identify a subset of the NBNC population at higher risk of HCC in hepatitis B virus endemic areas.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2020)

Wnt Activation as a Therapeutic Strategy in MedulloblastomaMedulloblastomas stratify to four main groups: Wnt, Shh, Group 3, and Group 4. Of these, patients harboring Wnt-driven tumors respond most favorably to standard-of-care treatment.Wnt antagonists have been shown to deregulate the blood-brain barrier, making Wnt tumors more accessible to treatment.Manoranjan and colleagues now suggest that Wnt signaling decreases self-renewal pathways that drive tumor propagation.Using patient-derived medulloblastoma-initiating cell lines from different subgroups and single-cell sequencing, they identified rare Wnt-responsive Group 3 and 4 cells.Treatment with Wnt3a or transfection with oncogenic b-catenin reduced the oncogenic properties of these rare cells.Wnt signaling thus exerted tumor suppressive effects on Group 3 and 4 medulloblastoma cells.Finally, they used a GSK3 inhibitor to activate Wnt signaling in Group 3 and 4 cells in vitro and in vivo, reducing cell growth and improving survival of xenografted mice.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2020)

Activation of STING (stimulator of interferon genes) protein is a promising immune modulatory strategy in cancer.However, all current STING agonists exhibit significant on-target toxicity in normal tissue, limiting their clinical use to intratumoral injection.To identify an improved agonist, Pan and colleagues screened a large library of small molecules for those capable of stimulating interferon production.Their lead molecule, MSA2, was orally active and well tolerated in vivo.MSA2 induced complete regression in a number of syngeneic tumor mouse models in a manner that persisted upon rechallenge.MSA2 also synergized with anti-PD-1 therapy in mouse tumor models previously shown to be resistant to anti-PD-1 therapy.Importantly, MSA2 exhibited selectivity for tumor tissue.MSA2 exists in equilibrium between its monomer and dimer.The dimer represents the active molecule.At physiological pH, monomeric MSA2 was favored, while at the pH of tumor cells, the active dimeric form was favored, contributing to its selectivity.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2020)

T-cell responses are impeded by progressive loss of T-cell function.Vardhana and colleagues showed that chronic antigen stimulation drives T-cell dysfunction by disrupting mitochondrial oxidative phosphorylation and ATP generation.In in vitro models of chronic T-cell stimulation versus a single stimulus, T cells failed to produce effector cytokines and upregulated markers of exhaustion.This phenotype was accompanied by reduced oxidative phosphorylation and reduced ATP.Mechanistically, reactive oxygen species (ROS) disrupted the electron transport chain.N-Acetylcysteine (NAC), a cell permeable form of cysteine and a building block of the cellular antioxidant glutathione, blocked elevated ROS in chronically stimulated T cells.NAC restored both oxidative phosphorylation and the function of T cells in vitro.Expanding chronically activated antitumor T cells in vitro with NAC led to recovered activity of the T cells and enhanced antitumoral activity against mouse cancer models.Expert Commentary: Controlling ROS in antitumor T cells restores oxidative phosphorylation capacity, improving T-cell function and tumoricidal activity.(Image courtesy of
Abstract PR09: Pharmacologic targeting of Gq reveals new pathways in uveal melanoma
Authors: Michael D. Onken, Carol M. Makepeace, Kevin M. Kaltenbronn, Stanley M. Kanai, Tyson D. Todd, Shiqi Wang, Thomas J. Broekelmann, Prabakar Kumar Rao, John A. Cooper, Kendall J. Blumer
Journal: Cancer Research (2020)

Abstract Constitutively activating mutations in GNAQ (Gαq) or GNA11 (Gα11) are the oncogenic drivers of uveal (eye) melanoma (UM), occurring in over 90% of tumors. We show that constitutively active Gαq in UM cells can be targeted by the cyclic depsipeptide FR900359 (FR). FR inhibits GDP/GTP exchange allosterically to trap constitutively active Gαq in inactive GDP-bound Gαβγ heterotrimers, and allosteric inhibition of other Gα subunits can be achieved by introduction of an FR binding site. In UM cells driven by constitutively active Gαq, FR inhibits second messenger signaling, arrests proliferation, and reinstates melanocytic differentiation. At higher doses, FR also induces apoptosis. FR has no effect on Gαq/11-wild-type UM cells. FR promotes UM cell differentiation by reactivating polycomb repressive complex 2 (PRC2)-mediated gene silencing, antagonized by a heretofore unrecognized effector system of constitutively active Gαq in UM. Constitutively active Gαq and PRC2 therefore provide important therapeutic targets for UM. Further, the development of FR analogs specific for other Gα subunit subtypes may provide novel therapeutic approaches for diseases driven by constitutively active Gα subunits or multiple G protein-coupled receptors where targeting a single receptor is ineffective. This abstract is also being presented as Poster A10. Citation Format: Michael D. Onken, Carol M. Makepeace, Kevin M. Kaltenbronn, Stanley M. Kanai, Tyson D. Todd, Shiqi Wang, Thomas J. Broekelmann, Prabakar Kumar Rao, John A. Cooper, Kendall J. Blumer. Pharmacologic targeting of Gq reveals new pathways in uveal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr PR09.
Abstract A23: Effects of anti-CTLA-4 and anti-PD-1 on memory T-cell differentiation and resistance to tumor relapse
Authors: Stephen Mok, Colm R. Duffy, Nana-Ama A. Anang, James P. Allison
Journal: Cancer Research (2020)

Abstract Both anti-CTLA-4 and anti-PD-1 mediate significant response rates in cancer patients. As a hallmark of successful immunotherapies, they also mediate durable responses that last for years. For example, anti-CTLA-4 mediates a 22% 10-year overall survival rate, while anti-PD-1 mediates a 34% 5-year overall survival rate. Because of the broader uses of immunotherapies, the number of patients who have tumor relapse also increases. About 25% of patients who initially responded to anti-PD-1 have tumor relapse within 24 months. However, the relationship between tumor relapse and long-term effect of immunotherapies is still not clear. The goal of this study is to understand the differential effect of anti-CTLA-4 and anti-PD-1 on memory T-cell differentiation in murine tumor models. By rechallenging mice with tumor cells that have had tumors previously eradicated by either treatment, our results have shown that anti-CTLA-4 induces a more durable memory antitumor response compared to that treated with anti-PD-1. By tracing the antigen-specific CD8 T-cells throughout the memory phase, anti-CTLA-4 increases the frequency and cytokine production of antigen-specific T cells compared with anti-PD-1. We have also found that anti-CTLA-4 induces the population of KLRG1+ effector CD8 T cells among the effectors compared with anti-PD-1 during rechallenge, despite the ratio between central memory and effectors remaining the same. Our studies enable us to identify the long-term effect of immunotherapies on immune system. Citation Format: Stephen Mok, Colm R. Duffy, Nana-Ama A. Anang, James P. Allison. Effects of anti-CTLA-4 and anti-PD-1 on memory T-cell differentiation and resistance to tumor relapse [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A23.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2020)

A new immunotherapy aims to activate the innate interferon response within tumors using drugs to stimulate STING (stimulator of interferon genes).While STING agonists were known to negatively impact T cells, Wu and colleagues demonstrate that this activity is intrinsic to T cells and does not require interferon induction.The authors generated a Sting1 S365A/S365A mutant mouse, lacking a phosphorylation site necessary for activating interferon.STING activation in macrophages induced a potent interferon response in T cells, the IFN response was muted, and other responses predominated associated with epigenetic regulation and cellular differentiation.Further, interferon-independent functions of STING caused T cells to die upon infiltration of tumors.Blocking STING activity specifically in T cells improved control of multiple transplanted tumors.Therefore, while STING activity in innate macrophages and dendritic cells promotes antitumor immunity, STING activity directly in T cells weakens their survival, promoting tumor immune resistance.Expert Commentary: Interferon-independent activities of STING disrupt survival of T cells in tumors and may support cancer immune evasion.(Image by Yancho Sabev from Wikimedia